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Gene therapy to improve vision

a technology of gene therapy and vision improvement, applied in the direction of genetic material ingredients, drug compositions, peptide/protein ingredients, etc., can solve the problems of limiting the quality of resulting vision, symptomatic and often suffer visual handicap dependence,

Inactive Publication Date: 2018-02-01
UCL BUSINESS PLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method for improving vision in patients with cone photoreceptor dysfunction or degeneration by introducing a nucleic acid that encodes a light-sensitive protein into healthy rod photoreceptors in the retina. This results in the expression of the light-sensitive protein and the extension of the range of light intensities to which the rod photoreceptor responds and the increase in the speed at which the rod photoreceptor responds to light. This method can be used to treat vision disorders that affect cones, the most important photoreceptors for color and fine detail, and can also create a "pseudo-fovea," a small patch of cone-like rods that can improve vision in patients with foveal cone dysfunction or loss.

Problems solved by technology

On the contrary, when cone dysfunction is present, patients are always symptomatic and often suffer visual handicap dependent on the degree of their cone dysfunction.
While patients with advanced AMD can be trained to fixate extra-foveally, the low refresh rate and the low bleaching threshold of rod cells limits the quality of resulting vision.

Method used

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  • Gene therapy to improve vision

Examples

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example 1

Methods for ArchT Experiments

[0106]Animals

[0107]Wild-type mice (C57BL / 6J) were purchased from Harlan Laboratories (Blackthorn, UK). CNGA3− / − and PDE6C− / − mice were bred in house. All mice were maintained under cyclic light (12 h light-dark) conditions; cage illumination was 7 foot-candles during the light cycle. All experiments were approved by the local Institutional Animal Care and Use Committees (UCL, London, UK) and conformed to the guidelines on the care and use of animals adopted by the Society for Neuroscience and the Association for Research in Vision and Ophthalmology (Rockville, Md.).

[0108]Plasmid Constructions, Viral Production and Injection Procedure

[0109]The transgene construct (ArchT-EGFP) was kindly provided by Prof Ed Boyden (MIT, USA) and contains the cDNA sequence of the ArchT gene fused to the fluorescent protein EGFP. The plasmids were packaged into AAV8 to generate recombinant AAV viral vectors, AAV8.hRho.ArchT-EGFP. Recombinant AAV8 vector was produced through ...

example 2

ArchT Expression in Rod Photoreceptors Confers the Ability to Respond with Rapid Non-Bleaching Responses

[0124]Rod-mediated vision is optimized for low light levels, including single photon detection. However, rods cannot match the rapid onset and recovery of cone responses to light (Fu et al., 2007, Pugh et al., 1999). This functional difference, useful to ensure reliable vision in different environments, becomes debilitating when cone-mediated vision is lost in conditions such as in age-related macular degeneration, when the densely packed cones in the fovea degenerate (de Jong 2006). It was investigated whether if rods could respond and recover more quickly to stimuli, this would help alleviate the functional impairment caused by the loss of cones.

[0125]A fast light-driven proton pump (ArchT) (Han et al., 2011) was expressed in rod photoreceptors. AAV8 particles carrying ArchT-EGFP under control of the Rhodopsin promoter (Rho) were injected subretinally in adult mice. Expression o...

example 3

ArchT-Expressing Rods Drive Sustained RGC Spiking at High Light Intensities and at Frequencies Approaching Those of Cone Photoreceptors

[0127]It was next investigated whether the circuitry driven by rods would be able to follow faster-than-normal rod-driven vision. Rod and cone pathways present some similarities and some striking differences and it is therefore not clear whether the rod circuitry can reliably sustain fast ‘cone-like’ transmission (Wässle et al., 2004). Rods have been shown to contact OFF ‘cone’ bipolar cells directly (Soucy et al., 1998 and Hack et al., 1999) and paired-pulse stimulation suggests that this alternative pathway may be as fast as the cone-to-OFF-bipolar one (Li et al., 2010). However, it is not clear how sustained this response can be and whether rod (ON) bipolar cells can also sustain fast transmission. Furthermore, rod synaptic terminals have different size and ultra-structural organization compared to cones and rod bipolar cells do not contact Retina...

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Abstract

The invention relates to the use of gene therapy vectors to improve vision by introducing into healthy rod photoreceptor cells of a patient suffering from cone photoreceptor dysfunction and / or degeneration a nucleic acid encoding a gene product that is light-sensitive and / or that modulates endogenous light-sensitive signaling in a photoreceptor cell, such that the range of light intensities to which the rod photoreceptor responds is extended and / or the speed at which the rod photoreceptor responds to light is increased.

Description

FIELD OF THE INVENTION[0001]The present invention relates to the use of gene therapy vectors to improve vision in patients.BACKGROUND OF THE INVENTION[0002]In many mammalian species including mice and humans, the number of rod photoreceptors that mediate vision under dim light outnumbers greatly that of cone photoreceptors (Curcio et al, 2000). However, in an industrialised world where illumination allows cones to operate throughout the day, rod-mediated vision is less important. Many patients with absent rod function from birth are identified only incidentally and, in fact, cannot recognize their abnormal vision (Dryja, 2000). On the contrary, when cone dysfunction is present, patients are always symptomatic and often suffer visual handicap dependent on the degree of their cone dysfunction. In some conditions, however, only (or mostly) the cones are lost or dysfunctional and rods remain relatively preserved. For example, achromatopsia is a severe hereditary retinal dystrophy with a...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12N15/86C07K14/705A61K38/17A61K48/00
CPCC12N15/86A61K48/0058A61K48/0075C07K14/705A61K38/177C12N2750/14143C12N2830/008A61P27/02
Inventor RIZZI, MATTEOALI, ROBINSMITH, ALEXANDERNISHIGUCHI, KOJI
Owner UCL BUSINESS PLC
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